Anti-Tuberculosis Bacteriophage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Anti-Tuberculosis Bacteriophage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
复制标题
DOI：
10.1007/s11095-017-2213-4
复制
发表时间：
2017-10-01
影响因子：
3.7
通讯作者：
Vehring, Reinhard
中科院分区：
文献类型：
--
作者：
Carrigy, Nicholas B.;Chang, Rachel Y.;Vehring, Reinhard
比较三种吸入装置对抗结核活性噬菌体D29滴度的降低和给药率。噬菌体D29裂解液扩增至11.8 +/- 0.3 log(10)（pfu/mL）滴度，用等渗盐水1:100稀释。过滤器捕获从三种吸入装置发出的雾化生理盐水D29制剂：1)振动网状雾化器；2)喷射雾化器；3)软雾吸入器。用代宿主耻垢分枝杆菌在多种稀释水平下进行三次全板菌斑测定，用于定量噬菌体滴度。振动网雾化器、喷射雾化器和软雾吸入器的滴度降低幅度分别为0.4 +/- 0.1、3.7 +/- 0.1和0.6 +/- 0.3 log(10)（pfu/mL）。振动网状雾化器的活性噬菌体递送率(3.3 × 10（8) +/- 0.8 × 10(8) pfu/min）显著高于喷射雾化器(5.4 × 10(4) +/- 1.3 × 10(4) pfu/min) （p < 0.01）。软雾吸入器每11.6 +/- 1.6 μ L前致动器剂量提供4.6x10(6) +/- 2.0x10(6) pfu。输送活性噬菌体需要谨慎选择吸入装置。在测试条件下，喷射雾化器不是雾化噬菌体D29的好选择，因为在液滴生产过程中可能会出现大量滴度降低。震动网喷雾器被推荐用于需要大量D29气溶胶的动物吸入研究，而软雾吸入器可能对D29气溶胶的自我管理有用。
To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices.Phage D29 lysate was amplified to a titer of 11.8 +/- 0.3 log(10)(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer.Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 +/- 0.1, 3.7 +/- 0.1, and 0.6 +/- 0.3 log(10)(pfu/mL). Active phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x10(8) +/- 0.8x10(8) pfu/min) than for the jet nebulizer (5.4x10(4) +/- 1.3x10(4) pfu/min). The soft mist inhaler delivered 4.6x10(6) +/- 2.0x10(6) pfu per 11.6 +/- 1.6 mu L ex-actuator dose.Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.